Page 1006 - Veterinary Immunology, 10th Edition

The IL-31 receptor is expressed on canine mononuclear cells,
VetBooks.ir keratinocytes, and dorsal root ganglia. In humans with AD or

allergic contact dermatitis, the level of IL-31 mRNA is higher in
atopic skin lesions than in normal skin. Thus the combination of

allergens and the presence of bacteria may stimulate T cells,
keratinocytes, and neurons to trigger the inflammation and pruritus
of atopic dermatitis using IL-31. The synthetic Janus kinase (JAK)
inhibitor oclacitinib maleate may reduce pruritus in many dogs and

cats with AD. It blocks signal transduction by JAK1 and JAK3 and
as a result inhibits the activities of IL-31 and several other
cytokines. It can therefore reduce both the pruritus and the severity
of the dermatitis and improve the quality of life for many of these

animals. Excessive blocking of IL-31 function may be undesirable
since IL-31 regulated genes are also involved in forming an intact
skin barrier, and IL-31 stimulates the production of antimicrobial
peptides (Box 30.1).

Box 30.1

Monoclonal Antibody Therapy for

Atopic Dermatitis

As noted in the text, interleukin-31(IL-31) is the major cause of the

severe itching observed in atopic dermatitis (AD) in dogs. The
production of IL-31 in affected skin can be inhibited by the JAK
inhibitor oclacitinib. It can also be neutralized by administration of
a caninized monoclonal antibody—Lokivetmab, directed

specifically at canine IL-31. The antibody is injected
subcutaneously. It binds to circulating IL-31 and inhibits its
binding to the IL-31 receptor. In double-blind, placebo-controlled
trials, a single dose has provided relief from itch and a reduction in

disease severity in dogs with chronic AD.

Michels GM, Ramsey DS, Walsh KF, et al. A blinded, randomized, placebo-controlled,
dose determination trial of lokivetmab (ZTS-00103289), a caninized, anti-canine IL-31
monoclonal antibody in client owned dogs with atopic dermatitis. Vet Dermatol 27: 478–
e129, 2016.

The Role of IgE

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